Plunging Platelets: Thrombocytopenia in the Pediatric Patient - Dr. Jayson Stoffman Pediatric Hematology/Oncology

Plunging Platelets: Thrombocytopenia
in the Pediatric Patient
Dr. Jayson Stoffman
Pediatric Hematology/Oncology

Presenter Disclosure
• Faculty / Speaker’s name: Dr. J. Stoffman

• Relationships with commercial interests:
   – Grants/Research Support: Daiichi Sankyo, Hoffman-La Roche
   – Speakers Bureau/Honoraria: None
   – Consulting Fees: Bayer Inc., Hoffman-La Roche Ltd.
   – Other: None

Learning Objectives
By the end of this presentation, the participant should
be able to:
1. Explain common causes of thrombocytopenia in
    children
2. Describe the presentation, clinical course, and
    treatment options for ITP in children

Thrombocytopenia in pediatrics
•   Pseudothrombocytopenia
•   Impaired production:
     – Marrow infiltration or failure
     – Congenital disorders: TAR, BSS, MYH9-related, WAS
•   Increased consumption:
     –   Hypersplenism
     –   Infection/illness
     –   Drug-induced
     –   Thrombosis
     –   Autoimmune condition – Evans syndrome, SLE, others…
     –   Microangiopathic hemolytic anemias – DIC, HUS, TTP
•   Immune thrombocytopenic purpura

This algorithm is intended for general guidance only, and should be used with appropriate clinical judgement.

Immune Thrombocytopenia Purpura
• Uncommon – incidence of 3-8 to 7.2-9.5/100 000
• A diagnosis of EXCLUSION
• Sudden onset of purpura and petechiae in an otherwise
  normal child with an otherwise normal physical
  examination
• Isolated thrombocytopenia on the CBC
   – Smear usually shows few large platelets with no other
     abnormalities

ITP – A tale of two conditions
SL – DOB April 2010             LM – DOB April 2012
• 1 month history of            •   Large bruise after minor injury
  increased bruising            •   Mild viral URTI 3 weeks before
• 1 nosebleed lasting 30 min    •   Platelet count 3
• Platelet count 2              •   3 weeks later – Plt count 37
• 3 weeks later – Plt count 3   •   18 months later – Plt count 118

The worst case scenario
AH – DOB May 2008
• 1 week history of purpura
• 1 day history of mucosal
  bleeding and altered LOC
• Platelet count 4

Intracranial hemorrhage
• 0.4-0.6% of all ITP
• UK experience: 14 cases of
  ICH over 20 years
• World literature 1970-99:
  54 reported ICH

What counts count?
•   Normal platelet count: 150 – 450 X 10e9/L
•   Thrombocytopenia: Plt < 100
•   < 50 – Increased risk of bleeding with trauma/surgery
•   < 20 – Petichiae and spontaneous bruising
•   < 10 – Increased risk of severe hemorrhage

Mechanism of thrombocytopenia in ITP is different

Important definitions (IWG)
• Remission: Plt count > 100

• Acute: < 3 months
• Persistent: 3-12 months
• Chronic: >12 months

Treatment considerations
• 80% of children will have spontaneous remission
   – Predictors poorly understood: younger age, bleeding at Dx
• Burden of illness and treatment are important
  considerations
• Shared decision making between physician and
  parents
   – Value of HRQoL measures in choices under investigation

Treatment options
First line            Second line
•   Observation       • Splenectomy
•   Corticosteroids   • TPO-RA
•   IvIg              • Rituximab
•   Anti-D

Treatment choices
• Patient/parent (and physician) preference and
  comfort
• Treatment profile
   – Likelihood of remission
   – Side effects
   – Route of administration

Key messages
• Thrombocytopenia in children results from increased
  consumption or decreased production, due to a
  variety of causes.
• ITP in children is generally a benign and self-limited
  condition, and treatment should be directed at
  symptom management for improved quality of life.

Key references
• Bennett CM et al (2018). Predictors of remission in children with newly diagnosed immune
  thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants.
  Pediatr Blood Cancer 65: e26736.
• Chaturvedi S et al (2018). Splenectomy for immune thrombocytopenia: down but not out. Blood 131: 1172-
  82.
• Cuker A (2018). Transitioning patients with immune thrombocytopenia to second-line therapy: Challenges
  and best practices. Am J Hematol 00:1-8 (https://doi.org/10.1002/ajh.25092).
• Grace RF et al (2018). Physician decision making in selection of second-line treatments in immune
  thrombocytopenia in children. Am J Hematol, accepted for publication (https://doi.org/10.1002/ajh.25110).
• Neunert C et al (2015). Severe bleeding events in adults and children with primary immune
  thrombocytopenia: a systematic review. J Thromb Haemost 13: 457-64.
• Schifferli A et al (2018). A comparative prospective observational study of children and adults with immune
  thrombocytopenia: 2-year follow-up. Am J Hematol 0: 1-9 (https://doi.org/10.1002/ajh.25086).

Thank you
jstoffman@cancercare.mb.ca